Genetic characteristics involved in COVID-19 severity. The CARGENCORS case-control study and meta-analysis.

Pre-existing coronary artery disease (CAD), and thrombotic, inflammatory, or virus infectivity response phenomena have been associated with COVID-19 disease severity. However, the association of candidate single nucleotide variants (SNVs) related to mechanisms of COVID-19 complications has been seldom analysed. Our aim was to test and validate the effect of candidate SNVs on COVID-19 severity.

-related muscular dystrophy: Identification of variants in alternative genes and personalized clinical translation.

Laminopathies are caused by rare alterations in , leading to a wide clinical spectrum. Though muscular dystrophy begins at early ages, disease progression is different in each patient. We investigated variability in laminopathy phenotypes by performing a targeted genetic analysis of patients diagnosed with -related muscular dystrophy to identify rare variants in alternative genes, thereby explaining phenotypic differences.

Reevaluation of ambiguous genetic variants in sudden unexplained deaths of a young cohort.

Sudden death cases in the young population remain without a conclusive cause of decease in almost 40% of cases. In these situations, cardiac arrhythmia of genetic origin is suspected as the most plausible cause of death. Molecular autopsy may reveal a genetic defect in up to 20% of families.

Unpredicted Aberrant Splicing Products Identified in Postmortem Sudden Cardiac Death Samples.

Molecular screening for pathogenic mutations in sudden cardiac death (SCD)-related genes is common practice for SCD cases. However, test results may lead to uncertainty because of the identification of variants of unknown significance (VUS) occurring in up to 70% of total identified variants due to a lack of experimental studies. Genetic variants affecting potential splice site variants are among the most difficult to interpret.

Post-mortem toxicology analysis in a young sudden cardiac death cohort.

Risk of sudden cardiac death (SCD) increases with age, and several studies have examined the impact of different drugs on cardiovascular function. However, few studies have integrated epidemiological drug consumption data and genetic background in the context of cardiac death. We performed a retrospective population-based study in forensic sudden death cases from a 9-year period in Catalonia.

Rare variants in genes encoding structural myocyte contribute to a thickened ventricular septum in sudden death population without ventricular alterations.

Unexpected cardiac deaths are a current challenge to healthcare systems. In adults, coronary artery disease and acquired cardiomyopathies are the most frequent causes of sudden cardiac death while in younger than 35 years old, the main cause is represented by non-ischemic diseases, usually inherited. Nowadays, around 10%-15% of unexpected deaths remain without a definite cause of decease after a complete autopsy, then classified as deaths potentially due to an inherited arrhythmia.

Discerning the Ambiguous Role of Missense Variants in Inherited Arrhythmogenic Syndromes.

The titin gene () is associated with several diseases, including inherited arrhythmias. Most of these diagnoses are attributed to rare variants encoding truncated forms, but missense variants represent a diagnostic challenge for clinical genetics. The proper interpretation of genetic data is critical for translation into the clinical setting.

High-quality RNA improves sensitivity of SARS-CoV-2 detection by colorimetric RT-LAMP.

The global SARS-CoV-2 pandemic requires a rapid, reliable, and user-friendly diagnostic test to help control the spread of the virus. Reverse transcription and quantitative PCR (RT-qPCR) is currently the gold standard method for SARS-CoV-2 detection. Here, we develop a protocol based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) and demonstrate increased sensitivity of this technique using fresh RNA extracts compared to RNA samples subjected to freezing/thawing cycles.

Early Identification of Prolonged QT Interval for Prevention of Sudden Infant Death.

Long QT syndrome is the main arrhythmogenic disease responsible for sudden death in infants, especially in the first days of life. Performing an electrocardiogram in newborns could enable early diagnosis and adoption of therapeutic measures focused on preventing lethal arrhythmogenic events. However, the inclusion of an electrocardiogram in neonatal screening protocols still remains a matter of discussion.

Malignant Arrhythmogenic Role Associated with : A Comprehensive Interpretation Focused on a Personalized Approach.

The gene encodes the muscle-specific splicing factor RNA-binding motif 20, a regulator of heart-specific alternative splicing. Nearly 40 potentially deleterious variants in have been reported in the last ten years, being found to be associated with highly arrhythmogenic events in familial dilated cardiomyopathy. Frequently, malignant arrhythmias can be a primary manifestation of disease.

Rare Variants Associated with Arrhythmogenic Cardiomyopathy: Reclassification Five Years Later.

Genetic interpretation of rare variants associated with arrhythmogenic cardiomyopathy (ACM) is essential due to their diagnostic implications. New data may relabel previous variant classifications, but how often reanalysis is necessary remains undefined. Five years ago, 39 rare ACM-related variants were identified in patients with features of cardiomyopathy.

Sudden Cardiac Death and Copy Number Variants: What Do We Know after 10 Years of Genetic Analysis?

Over the last ten years, analysis of copy number variants has increasingly been applied to the study of arrhythmogenic pathologies associated with sudden death, mainly due to significant advances in the field of massive genetic sequencing. Nevertheless, few published reports have focused on the prevalence of copy number variants associated with sudden cardiac death. As a result, the frequency of these genetic alterations in arrhythmogenic diseases as well as their genetic interpretation and clinical translation has not been established.

Short QT Syndrome: A Comprehensive Genetic Interpretation and Clinical Translation of Rare Variants.

Short QT syndrome, one of the most lethal entities associated with sudden cardiac death, is a rare genetic disease characterized by short QT intervals detected by electrocardiogram. Several genetic variants are causally linked to the disease, but there has yet to be a comprehensive analysis of variants among patients with short QT syndrome. To fill this gap, we performed an exhaustive study of variants currently catalogued as deleterious in short QT syndrome according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Personalized Interpretation and Clinical Translation of Genetic Variants Associated With Cardiomyopathies.

Cardiomyopathies are a heterogeneous group of inherited cardiac diseases characterized by progressive myocardium abnormalities associated with mechanical and/or electrical dysfunction. Massive genetic sequencing technologies allow a comprehensive genetic analysis to unravel the cause of disease. However, most identified genetic variants remain of unknown clinical significance due to incomplete penetrance and variable expressivity.

Molecular autopsy in a cohort of infants died suddenly at rest.

Sudden infant death syndrome is the leading cause of death during the first year of life. A large part of cases remains without a conclusive cause of death after complete autopsy. In these situations, cardiac arrhythmia of genetic origin is suspected as the most plausible cause of death.

Incomplete Penetrance and Variable Expressivity: Hallmarks in Channelopathies Associated with Sudden Cardiac Death.

Sudden cardiac death is defined as an unexpected decease of cardiac origin. In individuals under 35 years old, most of these deaths are due to familial arrhythmogenic syndromes of genetic origin, also known as channelopathies. These familial cardiac syndromes commonly follow an autosomal dominant pattern of inheritance.

Genotyping of single nucleotide polymorphisms related to attention-deficit hyperactivity disorder.

Pharmacological treatment of several diseases, such as attention-deficit hyperactivity disorder (ADHD), presents marked variability in efficiency and its adverse effects. The genotyping of specific single nucleotide polymorphisms (SNPs) can support the prediction of responses to drugs and the genetic risk of presenting comorbidities associated with ADHD. This study presents two rapid and affordable microarray-based strategies to discriminate three clinically important SNPs in genes ADRA2A, SL6CA2, and OPRM1 (rs1800544, rs5569, and rs1799971, respectively).

Acrosin activity is a suitable indicator of boar semen preservation at 17 °C when increasing environmental temperature and radiation.

The effect of increasing environmental temperature and radiation on the sperm quality and the field fertility of refrigerated seminal doses from AI boars (N = 30) was analyzed throughout four experimental months (from March through June). In each experimental month, analyses of sperm quality were performed at days 0, 1, 3, 5, 7, and 9 of refrigeration of seminal doses; pregnancy rate and litter size were evaluated using double monospermic inseminations of multiparous female animals using seminal doses at Days 1 to 2 and Days 3 to 4 of refrigeration. Sperm quality was assessed from the evaluation of conventional parameters of sperm concentration, sperm motility, sperm morphology, and sperm viability, and capacitation parameters of membrane lipid disorder, intracellular calcium content, and acrosin activity.

Epididymal maturation and ejaculation are key events for further in vitro capacitation of boar spermatozoa.

Mammalian spermatozoa acquire functionality during epididymal maturation, and the ability to penetrate and fertilize the oocyte during capacitation. The aim of this study was to assess the effects of epididymal maturation, ejaculation and in vitro capacitation on sperm viability, acrosome integrity, mitochondrial activity, membrane fluidity, and calcium influx, both as indicators of capacitation status and sperm motility. Results indicated that boar spermatozoa acquired the ability to move in the epididymal corpus; however, their motility was not linear until the ejaculation.

Glycocalyx characterisation and glycoprotein expression of Sus domesticus epididymal sperm surface samples.

The sperm surface is covered with a dense coating of carbohydrate-rich molecules. Many of these molecules are involved in the acquisition of fertilising ability. In the present study, eight lectins (i.

Study of the proacrosin-acrosin system in epididymal, ejaculated and in vitro capacitated boar spermatozoa.

The present study aimed to develop a set of sensitive assays to evaluate the presence of different isoforms, the activity degree, and the immunolocalisation of proacrosin-acrosin in sexually mature boars. The goal was to determine the proacrosin-acrosin status of boar spermatozoa throughout epididymal maturation, during ejaculation and after in vitro capacitation. In epididymal samples, proacrosin expression was high in all regions studied.

Impact of epididymal maturation, ejaculation and in vitro capacitation on tyrosine phosphorylation patterns exhibited of boar (Sus domesticus) spermatozoa.

Mammalian spermatozoa acquire functionality during epididymal maturation and ability to penetrate and fertilize the oocyte during capacitation. The aim of this study was to investigate the impact of epididymal maturation, ejaculation and capacitation on phosphotyrosine content of sperm proteins. Western blot, immunocytochemical and flow cytometry analyses demonstrated that epididymal maturation in vivo is associated with a progressive loss of phosphotyrosine residues of the sperm head followed by a subtle increase after in vitro capacitation.